Discussion

AZA is essential in managing AIH, often obviating the need for long-term prednisolone. Between 3%-13% of inflammatory bowel disease (IBD) and AIH patients will develop AZA-induced hepatotoxicity,3-5 which may be difficult to distinguish from AIH nonresponse or relapse without liver biopsy. In this setting, measuring thiopurine metabolites can provide diagnostic guidance. The finding of increased 6-MMP >5700 pmol/8 × 108 RBC with low or normal 6-TGN (“shunting”) is associated with hepatotoxicity and other side effects including nausea, anorexia, and influenza-like symptoms in IBD patients.5

This is the first reported adult case of allopurinol co-therapy in AIH for the management of AZA-induced hepatotoxicity. This strategy allowed our patient to discontinue prednisolone and avoid alternative immunosuppression. A study into the utility of measuring thiopurine metabolites identified AZA-induced hepatotoxicity, although the investigators found no role for measuring levels to monitor treatment response.3

In conclusion, in AIH patients who develop persistently significant ALT elevation after steroid discontinuation from a prednisolone-AZA regimen we recommend measuring thiopurine metabolites to distinguish between AZA-induced hepatotoxicity, nonadherence, or relapse and avoid repeat liver biopsy. AZA-induced hepatotoxicity should be suspected in patients with elevated 6-MMP (regardless of 6-TGN levels). The addition of allopurinol with appropriate AZA dose reduction may correct AZA-induced hepatoxicity and induce remission.